Antibody's specifity...

Mike Clark mrc7 at cam.ac.uk
Fri Jul 25 05:57:09 EST 2003


In article <3F2069C9.8010803 at NOSPAM.ucalgary.ca>, Bryan Heit
<URL:mailto:bjheit at NOSPAM.ucalgary.ca> wrote:
[snip]
> >
> > Included in there is analysis of a paper on antibodies to different
> > species of lysozyme in which I point out that "specificity" and
> > "affinity" are not easily related concepts.
> >
> I missed one point, although I don't know if this addresses the issue 
> you bring up.  They compare the affinity of the "antibody to the 
> antigen" vs. the affinity of the antibody to a "random panel of 
> antigens" (cell lysate I believe).  Specificity is measured as having 
> high affinity for the antigen with low affinity for random - but as I 
> mentioned earlier this may be specific (no pun intended) to their field.

No they looked at the binding of for example Hen Egg Lysozyme versus Turkey
Egg Lysozyme versus Quail Egg Lysozyme, versus a peptide.

My point is that as they altered the affinity of the antibody for one these
antigens the affinity for the others varies, sometimes higher, sometimes
lower. So if you define the specificity as an ability to tell two antigens
apart, which is a common requirement for a specific antibody, then the
highest affinity antibody is not necessarily the most specific.

> 
> > Yes but that is also partly because of a process of selection. The
> > frequency of B-cells making an antibody of any given specifity might be
> > low initially but it can be enhanced through selection and clonal
> > expansion. 
> >
> >What of T-independent immune responses, are they not also specific?
> >
> Never claimed they aren't.  But AFAIK these antibodies still go through 
> affinity maturation and thus gain greater affinity compared to the 
> initial, naive B-cells.
> 

Many antibodies to T-independent antigens show no somatic mutation and no
affinity maturation.

> > Look I'll give another example.
> >
> >I inject a mouse with human IgG as an antigen, and get back some
> >monoclonals which react with human IgG1, IgG2, IgG3 and IgG4 equally. Other
> >monoclonals react only with IgG1 but not with IgG2 3 or 4, and other
> >monoclonals react only with the allotype G1m(1,17) but not G1m(3).
> >
> >So which of these monoclonal antibodies do you consider  specific and which
> >are not specific? 
> >
> But in this case it is more likely the multi-reacting antibodies are 
> identifying shared epitopes between the different sub-classes.  For 
> those antibodies I would say that they are specific to a shared epitope. 
>  Considering the high degree of homology between the different IgG's it 
> is more then likely that they would be recognizing area's with 100% 
> protein homology.

Yes but you have already argued using the example of adhesion molecules
that antibodies rarely cross react between similar structures even when
they share strong amino acid homology. I've just given the opposite
example. I think the difference is one of selection of the antibodies in
the first place. If you select for known cross-reacting antibodies you
can find them, and if you select against known cross-reacting antibodies
you can also find them. But they are all antibodies.

> 
> > <snip>
> >
> >[snip] Must rush now. I'll deal with your other points tomorrow, but the
> >Tour de France beckons.........
> >  

Another exciting finish to todays stage, definitely one of the best tours
of recent years.

> > 
> Wouldn't worry about it - I'll probably miss your post as I'm leaving 
> for a week of SCUBA Friday.

Hope you have a good trip.

> Besides, we've gone a long way from the  origonal question (can I make
> one antibody that recognises 2 distinct  and unrelated proteins).  That
> said, I would recommend the origonal  poster listen to you, as you
> obviously know more about this then I...
> 
> Bryan
> 
> 
Cheers,

Mike Clark,                        <URL:http://www.path.cam.ac.uk/~mrc7/>
-- 
M.R. Clark, PhD. Division of Immunology
Cambridge University, Dept. Pathology
Tennis Court Rd., Cambridge CB2 1QP
Tel.+44 1223 333705  Fax.+44 1223 333875




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